Diabetes and fatty liver: insulin is not left alone; meet glucagone resistance

Researchers from the University of Copenhagen are introducing a new biological concept in the fight against diabetes: glucagon resistance. Glucagon resistance or decreased sensitivity to the hormone glucagon increases the risk of type 2 diabetes. New research shows that glucagon resistance is particularly pronounced in people with fatty liver, and this may be the key to understanding the link between fatty liver and diabetes. Up to one in four Danes has an unhealthy accumulation of fat in the liver, also known as steathosis. Another name for the condition is non-alcoholic fatty liver disease (NAFLD). Nonalcoholic fatty liver disease is a spectrum of hepatic diseases associated with metabolic and cardiovascular disorders, such as obesity, insulin resistance, hypertension, dyslipidemia and type 2 diabetes. Fatty liver is rarely the cause of symptoms in itself, but people with fatty liver have an increased risk of developing diabetes. Exactly how the two diseases are linked has, however, so far been unknown.

Now, a new study from the Faculty of Health and Medical Sciences at the University of Copenhagen shows that people with fatty liver have reduced sensitivity to glucagon which increases the glucagon secretion and leads to increased amounts of glucagon in the blood. The same is seen in patients with type 2 diabetes, the vast majority of whom have increased fat in the liver. The reduced glucagon sensitivity means that the secretion of glucagon is increased via a so-called feedback system between the liver and the pancreas. An elevated level of glucagon is undesirable as it increases sugar production in the liver and thus creates a high blood sugar level. With the study, the researchers are introducing an entirely new concept within the field of diabetes: glucagon resistance. They believe that the concept is so fundamental to the understanding of diabetes that it should not be limited to laboratories and research environments.

Nicolai Wewer Albrechtsen, Assistant Professor at the Novo Nordisk Center for Protein Research and at the Department of Clinical Biochemistry, explained: “Glucagon resistance is an entirely new biological concept that we will include in the future teaching of medical students, just as we do today with insulin resistance. The decreased glucagon sensitivity may help to explain the connection between fatty liver and type 2 diabetes. And with new knowledge come new opportunities. If you can detect decreased glucagon sensitivity, you can start treatment earlier. That way, you can stop the glucagon level and thus the blood sugar from running wild. Our study points to a new biomarker (the glucagon-alanine index) that may be useful in identifying persons with impaired glucagon sensitivity. If we can detect glucagon resistance from a blood test, we can start treatment early and thus prevent the development of type 2 diabetes”.

The treatment for fatty liver consists primarily of weight loss and a carbohydrate-poor diet, which will limit the amount of fat in the liver. With these new notions, it might also include drugs that go in and inhibit the hormone glucagon.

  • Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.

Scientific references

Winther-Sørensen M, Galsgaard K et al. Mol Metab. 2020 Sep 13:101080. 

Bisgaard Bengtsen M et al. J Clin Endocrinol Metab. 2020 Sep 14:dgaa645.

Papazafiropoulou AK, Melidonis A et al. Curr Pharm Des. 2020 Sep 9.

Informazioni su Dott. Gianfrancesco Cormaci 2479 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it